Supportive Care in Cancer

, Volume 14, Issue 6, pp 566–572 | Cite as

Amifostine in the management of radiation-induced and chemo-induced mucositis

  • Rene-Jean Bensadoun
  • Mark M. Schubert
  • Rajesh V. Lalla
  • Dorothy Keefe
Review Article

Abstract

Introduction

Mucositis is a significant complication of cancer therapy, with important clinical and economic implications. In June 2005, the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) conducted an evidence-based update review of the literature on mucositis. The goal of this literature review is to update previously published guidelines for the management of mucositis.

Results

This article reports the findings of the subgroup charged with reviewing the literature related to amifostine.

Keywords

Amifostine Mucositis Radiotheraphy Chemotheraphy 

Notes

Acknowledgement

The authors thank Mr. Ronald D. Hutchins, University of Texas M.D. Anderson Cancer Center, for conducting the literature search.

References

  1. 1.
    Antonadou D (2002) Radiotherapy or chemotherapy followed by radiotherapy with or without amifostine in locally advanced lung cancer. Semin Radiat Oncol 12:50–58CrossRefPubMedGoogle Scholar
  2. 2.
    Antonadou D, Pepelassi M, Synodinou M, Puglisi M, Throuvalas N (2002) Prophylactic use of amifostine to prevent radiochemotherapy-induced mucositis and xerostomia in head-and-neck cancer. Int J Radiat Oncol Biol Phys 52:739–747CrossRefPubMedGoogle Scholar
  3. 3.
    Antonadou D, Throuvalas N, Petridis A, Bolanos N, Sagriotis A, Synodinou M (2003) Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non-small-cell lung cancer. Int J Radiat Oncol Biol Phys 57:402–408CrossRefPubMedGoogle Scholar
  4. 4.
    Arquette M, Wasserman T, Govindan R, Garfield D, Senzer N, Gillenwater H, Socinski M (2002) Phase II evaluation of amifostine as an esophageal mucosal protectant in the treatment of limited-stage small cell lung cancer with chemotherapy and twice-daily radiation. Semin Radiat Oncol 12:59–61CrossRefPubMedGoogle Scholar
  5. 5.
    Athanassiou H, Antonadou D, Coliarakis N, Kouveli A, Synodinou M, Paraskevaidis M, Sarris G, Georgakopoulos GR, Panousaki K, Karageorgis P, Throuvalas N, Oncology Hellenic Group (2003) Protective effect of amifostine during fractionated radiotherapy in patients with pelvic carcinomas: results of a randomized trial. Int J Radiat Oncol Biol Phys 56:1154–1160CrossRefPubMedGoogle Scholar
  6. 6.
    Bardet E, Martin L, Calais G, Tuchais C, Bourhis J, Rhein B, Feham N, Alfonsi M (2002) Preliminary data of the GORTEC 2000–02 phase III trial comparing intravenous and subcutaneous administration of amifostine for head and neck tumors treated by external radiotherapy. Semin Oncol 29:57–60CrossRefPubMedGoogle Scholar
  7. 7.
    Benesch M, McDonald GB, Schubert M, Appelbaum FR, Deeg HJ (2003) Lack of cytoprotective effect of amifostine following HLA-identical sibling transplantation for advanced myelodysplastic syndrome (MDS): a pilot study. Bone Marrow Transplant 32:1071–1075CrossRefPubMedGoogle Scholar
  8. 8.
    Ben-Josef E, Han S, Tobi M, Shaw LM, Bonner HS, Vargas BJ, Prokop S, Stamos B, Kelly L, Biggar S, Kaplan I (2002) A pilot study of topical intrarectal application of amifostine for prevention of late radiation rectal injury. Int J Radiat Oncol Biol Phys 53:1160–1164CrossRefPubMedGoogle Scholar
  9. 9.
    Ben-Josef E, Han S, Tobi M, Vargas BJ, Stamos B, Kelly L, Biggar S, Kaplan I (2002) Intrarectal application of amifostine for the prevention of radiation-induced rectal injury. Semin Radiat Oncol 12:81–85CrossRefPubMedGoogle Scholar
  10. 10.
    Bonner HS, Shaw LM (2002) New dosing regimens for amifostine: a pilot study to compare the relative bioavailability of oral and subcutaneous administration with intravenous infusion. J Clin Pharmacol 42(2):166–174CrossRefPubMedGoogle Scholar
  11. 11.
    Bourhis J, Thephamongkhol K, Pignon JP (2004) Randomized trials of amifostine and radiotherapy: effect on survival? Semin Oncol 31:62–66CrossRefPubMedGoogle Scholar
  12. 12.
    Brizel DM, Overgaard J (2003) Does amifostine have a role in chemoradiation treatment? Lancet Oncol 4:378–381CrossRefPubMedGoogle Scholar
  13. 13.
    Buntzel J, Glatzel M, Kuttner K, Weinaug R, Frohlich D (2002) Amifostine in simultaneous radiochemotherapy of advanced head and neck cancer. Semin Radiat Oncol 12:4–13CrossRefPubMedGoogle Scholar
  14. 14.
    Hadorn DC, Baker D, Hodges JS et al (1996) Rating the quality of evidence for clinical practice guidelines. J Clin Epidemiol 49:749–754CrossRefPubMedGoogle Scholar
  15. 15.
    Hwang WY, Koh LP, Ng HJ, Tan PH, Chuah CT, Fook SC, Chow H, Tan KW, Wong C, Tan CH, Goh YT (2004) A randomized trial of amifostine as a cytoprotectant for patients receiving myeloablative therapy for allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant 34:51–56CrossRefPubMedGoogle Scholar
  16. 16.
    Jantunen E, Kuittinen T, Nousiainen T (2002) A pilot study on feasibility and efficacy of amifostine preceding high-dose melphalan with autologous stem cell support in myeloma patients. Leuk Lymphoma 43:1961–1965CrossRefPubMedGoogle Scholar
  17. 17.
    Komaki R, Lee JS, Kaplan B, Allen P, Kelly JF, Liao Z, Stevens CW, Fossella FV, Zinner R, Papadimitrakopoulou V, Khuri F, Glisson B, Pisters K, Kurie J, Herbst R, Milas L, Ro J, Thames HD, Hong WK, Cox JD (2002) Randomized phase III study of chemoradiation with or without amifostine for patients with favorable performance status inoperable stage II–III non-small cell lung cancer: preliminary results. Semin Radiat Oncol 12:46–49CrossRefPubMedGoogle Scholar
  18. 18.
    Koukourakis MI, Simopoulos C, Minopoulos G, Patlakas G, Polychronidis A, Limberis V, Romanides K, Pitiacoudis M, Manolas C (2003) Amifostine before chemotherapy: improved tolerance profile of the subcutaneous over the intravenous route. Clin Cancer Res 15:3288–3293Google Scholar
  19. 19.
    Kouloulias VE, Kouvaris JR, Kokakis JD, Kostakopoulos A, Mallas E, Metafa A, Vlahos LJ (2004) Impact on cytoprotective efficacy of intermediate interval between amifostine administration and radiotherapy: a retrospective analysis. Int J Radiat Oncol Biol Phys 59:1148–1156CrossRefPubMedGoogle Scholar
  20. 20.
    Kouvaris J, Kouloulias V, Kokakis J, Matsopoulos G, Balafouta M, Miliadou A, Vlahos L (2002) Cytoprotective effect of amifostine in radiation-induced acute mucositis—a retrospective analysis. Onkologie 25:364–369CrossRefPubMedGoogle Scholar
  21. 21.
    Kouvaris J, Kouloulias V, Malas E, Antypas C, Kokakis J, Michopoulos S, Matsopoulos G, Vlahos L (2003) Amifostine as radioprotective agent for the rectal mucosa during irradiation of pelvic tumors. A phase II randomized study using various toxicity scales and rectosigmoidoscopy. Strahlenther Onkol 179:167–174CrossRefPubMedGoogle Scholar
  22. 22.
    Leong SS, Tan EH, Fong KW, Wilder-Smith E, Ong YK, Tai BC, Chew L, Lim SH, Wee J, Lee KM, Foo KF, Ang P, Ang PT (2003) Randomized double-blind trial of combined modality treatment with or without amifostine in unresectable stage III non-small-cell lung cancer. J Clin Oncol 21:1767–1774CrossRefPubMedGoogle Scholar
  23. 23.
    Lorusso D, Ferrandina G, Greggi S, Gadducci A, Pignata S, Tateo S, Biamonte R, Manzione L, Di Vagno G, Ferrau’ F, Scambia G, Multicenter Italian Trials in Ovarian Cancer investigators (2003) Phase III multicenter randomized trial of Amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients. Ann Oncol 14(7):1086–1093CrossRefPubMedGoogle Scholar
  24. 24.
    Martin LM, Moran A, Damour MD, Piot G, Oudinot P (2004) Amifostine (A) reduces acute mucosal toxicity of accelerated radiotherapy (ART) and Carboplatin (CBP) in locally advanced head and neck cancer (HNSC). ASCO Annual Meeting Proceedings. J Clin Oncol 22(14S):5566Google Scholar
  25. 25.
    Movsas B, Scott C, Langer C, Werner-Wasik M, Nicolaou N, Komaki R, Machtay M, Smith C, Axelrod R, Sarna L, Wasserman T, Byhardt R (2005) Randomized trial of amifostine in locally advanced non-small-cell lung cancer patients receiving chemotherapy and hyperfractionated radiation: radiation therapy oncology group trial 98-01. J Clin Oncol 23:2145–2154CrossRefPubMedGoogle Scholar
  26. 26.
    Myerson R (2002) Rationale for a phase I/II radiation dose-escalation study with concurrent amifostine (Ethyol) and infusional 5-FU chemotherapy for preoperative treatment of unresectable or locally recurrent rectal carcinoma. Semin Radiat Oncol 12:86–90CrossRefPubMedGoogle Scholar
  27. 27.
    Myerson R, Zobeiri I, Birnbaum E, Dietz D, Fleshman J, Kodner I, Picus J, Ratkin G (2002) Early results from a phase I/II radiation dose-escalation study with concurrent amifostine and infusional 5-fluorouracil chemotherapy for preoperative treatment of unresectable or locally recurrent rectal carcinoma. Semin Oncol 29:29–33CrossRefPubMedGoogle Scholar
  28. 28.
    Nicolatou-Galitis O, Sotiropoulou-Lontou A, Velegraki A, Pissakas G, Kolitsi G, Kyprianou K, Kouloulias V, Papanikolaou I, Yiotakis I, Dardoufas K (2003) Oral candidiasis in head and neck cancer patients receiving radiotherapy with amifostine cytoprotection. Oral Oncol 39:397–401CrossRefPubMedGoogle Scholar
  29. 29.
    Rubenstein EB, Peterson DE, Schubert MM et al (2004) Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis. Cancer 100:2026–2046CrossRefPubMedGoogle Scholar
  30. 30.
    Schuchter LM, Hensley ML, Meropol NJ et al (2002) 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants : clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 20:2895–2903CrossRefPubMedGoogle Scholar
  31. 31.
    Senzer N (2002) A phase III randomized evaluation of amifostine in stage IIIA/IIIB non-small cell lung cancer patients receiving concurrent carboplatin, paclitaxel, and radiation therapy followed by gemcitabine and cisplatin intensification: preliminary findings. Semin Oncol 29:38–41CrossRefPubMedGoogle Scholar
  32. 32.
    Somerfield MR, Padberg JR, Pfister DG et al (2000) ASCO clinical practice guidelines: process, progress, pitfalls, and prospects. Class Pap Curr Comments 4:881–886Google Scholar
  33. 33.
    Sonis ST, Elting LS, Keefe D et al (2004) Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 100:1995–2025CrossRefPubMedGoogle Scholar
  34. 34.
    Spath-Schwalbe E, Lange C, Genvresse I, Kruger L, Eucker J, Schweigert M, Sezer O, Budach V, Possinger K (2002) Influence of amifostine on toxicity of CHOP in elderly patients with aggressive non-Hodgkin’s lymphoma—a phase II study. Anticancer Drugs 13:395–403CrossRefPubMedGoogle Scholar
  35. 35.
    Spencer A, Horvath N, Gibson J, Prince HM, Herrmann R, Bashford J, Joske D, Grigg A, McKendrick J, Prosser I, Lowenthal R, Deveridge S, Taylor K, Australasian Leukemia and Lymphoma Group (2005) Prospective randomised trial of amifostine cytoprotection in myeloma patients undergoing high-dose melphalan conditioned autologous stem cell transplantation. Bone Marrow Transplant 35:971–977CrossRefPubMedGoogle Scholar
  36. 36.
    Stokman MA, Wachters FM, Koopmans P, Burgerhof JG, Groen HJ, Spijkervet FK, Uges DR, Hospers GA (2004) Outcome of local application of amifostine (WR-1065) on epirubicin-induced oral mucositis. A phase II study. Anticancer Res 24:3263–3267PubMedGoogle Scholar
  37. 37.
    Suntharalingam M, Jaboin J, Taylor R, Wolf J, Banglore M, Van Echo D, Ord R (2004) The evaluation of amifostine for mucosal protection in patients with advanced loco-regional squamous cell carcinomas of the head and neck (SCCHN) treated with concurrent weekly carboplatin, paclitaxel, and daily radiotherapy (RT). Semin Oncol 31:2–7CrossRefPubMedGoogle Scholar
  38. 38.
    Thieblemont C, Dumontet C, Saad H, Roch N, Bouafia F, Arnaud P, Hequet O, Espinouse D, Salles G, Roy P, Eljaafari-Corbin A, Du Manoir-Baumgarten C, Coiffier B (2002) Amifostine reduces mucosal damage after high-dose melphalan conditioning and autologous peripheral blood progenitor cell transplantation for patients with multiple myeloma. Bone Marrow Transplant 30:769–775CrossRefPubMedGoogle Scholar
  39. 39.
    Trotti A, Bellm LA, Epstein JB, Frame D, Fuchs HJ, Gwede CK, Komaroff E, Nalysnyk L, Zilberberg MD (2003) Mucositis incidence, severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy: a systematic literature review. Radiother Oncol 66(3):253–262CrossRefPubMedGoogle Scholar
  40. 40.
    Tsavaris N, Kosmas C, Vadiaka M, Zonios D, Papalambros E, Papantoniou N, Margaris H, Zografos G, Rokana S, Retalis G, Koufos C (2003) Amifostine, in a reduced dose, protects against severe diarrhea associated with weekly fluorouracil and folinic acid chemotherapy in advanced colorectal cancer: a pilot study. J Pain Symptom Manage 26:849–854CrossRefPubMedGoogle Scholar
  41. 41.
    Vacha P, Fehlauer F, Mahlmann B, Marx M, Hinke A, Sommer K, Richter E, Feyerabend T (2003) Randomized phase III trial of postoperative radiochemotherapy +/− amifostine in head and neck cancer. Is there evidence for radioprotection? Strahlenther Onkol 179:385–389PubMedGoogle Scholar
  42. 42.
    Wang R, Kagan R, Tome M (2004) Subcutaneous amifostine during radiation or chemoradiation for the treatment of head and neck cancers. ASCO Annual Meeting Proceedings. J Clin Oncol 22(14S): 8154Google Scholar
  43. 43.
    Werner-Wasik M, Axelrod RS, Friedland DP, Hauck W, Rose LJ, Chapman AE, Grubbs S, Deshields M, Curran WJ (2002) Phase II trial of twice weekly amifostine in patients with non-small cell lung cancer treated with chemoradiotherapy. Semin Radiat Oncol 12:34–39CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Rene-Jean Bensadoun
    • 1
  • Mark M. Schubert
    • 2
  • Rajesh V. Lalla
    • 3
  • Dorothy Keefe
    • 4
  1. 1.Department of Radiation OncologyCentre Antoine-LacassagneNiceFrance
  2. 2.Department of Oral MedicineUniversity of Washington, Oral Medicine Service, Seattle Cancer Care AllianceSeattleUSA
  3. 3.Department of Oral Health and Diagnostic Sciences MC1605University of Connecticut Health CenterFarmingtonUSA
  4. 4.Department of MedicineUniversity of AdelaideAdelaideSouth Australia

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